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AJNR - American Journal of Neuroradiology

Published ahead of print on November 1, 2007
doi: 10.3174/ajnr.A0791

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American Journal of Neuroradiology 29:308-313, February 2008
© 2008 American Society of Neuroradiology

PEDIATRICS

Apparent Diffusion Coefficient Reveals Gray and White Matter Disease, and T2 Mapping Detects White Matter Disease in the Brain in Feline Alpha-Mannosidosis

C.H. Vite^a, S. Magnitsky^b, D. Aleman^a, P. O’Donnell^a, K. Cullen^a, W. Ding^a, S. Pickup^b, J.H. Wolfe^c and H. Poptani^b

^a W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pa
^b Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, Pa
^c Stokes Institute, Children’s Hospital of Philadelphia, Philadelphia, Pa

Please address correspondence to Charles H. Vite, DVM, PhD, Section of Neurology, Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3850 Spruce St, Philadelphia, PA 19105; e-mail: vite{at}vet.upenn.edu

BACKGROUND AND PURPOSE: Methods to locate and identify brain pathology are critical for monitoring disease progression and for evaluating the efficacy of therapeutic intervention. The purpose of this study was to detect cell swelling, abnormal myelin, and astrogliosis in the feline model of the lysosomal storage disease -mannosidosis (AMD) by using diffusion and T2 mapping.

MATERIALS AND METHODS: Average apparent diffusion coefficient (ADC_av) and T2 were measured by imaging the brains of five 16-week-old cats with feline AMD on a 4.7T magnet. ADC_av and T2 data from affected cats were compared with data from age-matched normal cats. Brains were collected from both affected and normal cats following imaging, and histology was compared with quantitative imaging data.

RESULTS: Gray matter from AMD cats demonstrated a 13%–15% decrease in ADC_av compared with that in normal cats. White matter from AMD cats exhibited an 11%–16% decrease in ADC_av and a 5%–12% increase in T2 values compared with those in normal control cats. Histologic evidence of neuronal and glial swelling, abnormal myelin, and astrogliosis was consistent with changes in ADC_av and T2.

CONCLUSION: ADC_av and T2 data can be used to quantify differences in the gray and white matter in the feline AMD brain and may serve as surrogate markers of neuronal swelling, abnormal myelin, and astrogliosis associated with this disease. These studies may be helpful in assessing the efficacy of experimental therapies for central nervous system disease associated with lysosomal storage diseases.